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Dipyrrolylquinoxalines: Efficient Sensors for Fluoride Anion in Organic Solution Christopher B. Black, Bruno Andrioletti, Andrew C. Try, Cristina Ruiperez, and Jonathan L. Sessler* Department of Chemistry and Biochemistry The UniVersity of Texas at Austin Austin, Texas 78712-1167 ReceiVed July 21, 1999 ReVised Manuscript ReceiVed September 16, 1999 In recent decades, supramolecular chemists have devoted considerable effort to developing systems capable of recognizing, sensing, and transporting negatively charged species.1 Among the range of biologically important anions, fluoride is of particular interest due to its established role in preventing dental caries.2 Fluoride anion is also being explored extensively as a treatment for osteoporosis3,4 and, on a less salubrious level, can lead to fluorosis,5-7 a type of fluoride toxicity that generally manifests itself clinically in terms of increasing bone density. This diversity of function, both beneficial and otherwise, makes the problem of fluoride anion detection one of considerable current interest. While traditional methods of fluoride anion analysis such as ion selective electrodes and 19F NMR spectroscopy remain important, there is mounting incentive to find alternative means of analysis, including those based on the use of specific chemosensors.8 Particularly useful would be systems that can recognize fluoride anion in solution and signal its presence via an easy-to-detect optical signature. In the past few years, we and others have proposed a wide range of anion sensors (sapphyrins,9 calixpyrroles,10,11 polyamines,12-15 guanidinium,16,17 etc.) that present varying degrees of affinity (and selectivity) toward anions such as F-, Cl-, H2PO4-, and carboxylates. Unfortunately, and despite considerable effort, a need for good anion sensors remains. This is particularly true in the case of fluoride anion where few, if any, easy-to-use signaling agents exist.18 Our recent experience with polypyrrole(1) Dietrich, B.; Hosseini, M. W. In Supramolecular Chemistry of Anions; Bianchi, A., Bowman-James, K., Garcı´a-Espan˜a, E., Eds.; Wiley-VCH: New York, 1997; pp 45-62. (2) Kirk, K. L. Biochemistry of the Halogens and Inorganic Halides; Plenum Press: New York, 1991; p 58. (3) Riggs, B. L. Bone and Mineral Research, Annual 2; Elsevier: Amsterdam, 1984; pp 366-393. (4) Kleerekoper, M. Endocrinol. Metab. Clin. North Am. 1998, 27, 441. (5) Wiseman, A. Handbook of Experimental Pharmacology XX/2, Part 2; Springer-Verlag: Berlin, 1970; pp 48-97. (6) Weatherall, J. A. Pharmacology of Fluorides. In Handbook of Experimental Pharmacology XX/1, Part 1; Springer-Verlag: Berlin, 1969; pp 141172. (7) Dreisbuch, R. H. Handbook of Poisoning; Lange Medical Publishers: Los Altos, CA, 1980. (8) Chemosensors of Ion and Molecular Recognition; Desvergne, J.-P., Czarnik, A. W., Eds., NATO ASI Series, Series C; Kluwer Academic Press: Dordrecht, the Netherlands, 1997; Vol. 492. (9) Sessler, J. L.; Andrievsky, A.; Genge, J. W. In AdVances in Supramolecular Chemistry; Lehn, J. M., Ed.; JAI Press Inc.: Greenwich, CT, 1997; Vol. 4, pp 97-142. (10) Gale, P. A.; Sessler, J. L.; Kra´l, V. K.; Lynch, V. M. J. Am. Chem. Soc. 1996, 118, 5140. (11) Sessler, J. L.; Gale, P. A.; Genge, J. W. Chem. Eur. J. 1998, 4, 1095. (12) Dietrich, B.; Hosseini, M. W.; Lehn, J. M.; Sessions, R. B. J. Am. Chem. Soc. 1981, 103, 1282. (13) Hosseini, M. W.; Lehn, J. M. HelV. Chim. Acta 1988, 71, 749. (14) Huston, M. E.; Akkaya, E. U.; Czarnik, A. W. J. Am. Chem. Soc. 1989, 111, 8735. (15) Czarnik, A. W. Acc. Chem. Res. 1994, 27, 302. (16) Dietrich, B.; Fyles, D. L.; Fyles, T. M.; Lehn, J.-M. HelV. Chim. Acta 1979, 62, 2763. (17) Metzger, A.; Lynch, V. M.; Anslyn, E. V. Angew. Chem., Int. Ed. Engl. 1997, 36, 862.
Figure 1. Proposed mode of anion binding and sensing. Recognition of, for instance, fluoride anion, is expected to perturb the orbital overlap between the pyrrole and quinoxaline subunits, thereby changing the optical characteristics of the latter.
Scheme 1
based anion binding agents led us to consider that pyrrolic systems containing a built-in chromophore might give rise to useful anion sensors. Our current investigations utilize the easy-to-prepare 2,3dipyrrol-2′-ylquinoxaline 1. While known in the literature since 1911,19 to the best of our knowledge, this particular entity has never been considered as being a possible colorimetric anion sensor. It contains two pyrrole NH groups that could function as anion binding moeities and a built-in quinoxaline ring that might serve as a colorimetric reporter of any binding events. As illustrated in Figure 1, this putative sensing system is expected to operate through a combination of electronic and conformational effects. The preparation of 1 involves condensing oxalyl chloride with pyrrole at -80 °C as described first by Oddo19 and later refined by Behr.20 Subsequent reaction between the resulting 2,3-dipyrrol2′-ylethanedione 2 with o-phenylenediamine in acetic acid at reflux leads to 2,3-dipyrrol-2′-ylquinoxaline 1 in excellent yield (Scheme 1). By modifying this procedure and using other 1,2diaminobenzenes, a wide range of 2,3-dipyrrol-2′-ylquinoxaline derivatives, possessing various electron-withdrawing or -donating groups, may, in principle, be prepared. In this paper we describe the synthesis of 2,3-dipyrrol-2′-yl-6-nitroquinoxaline 3 and the anion binding properties of it, its “parent” 1, and the control systems, quinoxaline, 2,3-dipyrrol-2′-ylethanedione 2, and the monotrimethylsilylethoxymethyl (SEM)-protected species 4. The ability of the dipyrrole systems 1 and 3 to coordinate to F-, Cl-, and H2PO4- (as tetrabutylammonium salts) was inves(18) For a recent report of fluorescence-based F- detection using boronic acids, see: Cooper, C. R.; Spencer, N.; James, T. D. Chem. Commun. 1998, 1365. (19) Oddo, B. Gazz. Chim. Ital. 1911, 41, 248. (20) Behr, D.; Branda¨nge, S.; Lindstro¨m, B. Acta Chem. Scand. 1973, 27, 2411. (21) UV/vis titrations: All stock solutions were prepared in dichloromethane. Spectra were collected on a Beckman DU-640 UV/vis spectrophotometer. Since 2 does not fluoresce significantly, yet maintains a relatively large extinction coefficient, anion binding titrations were carried out by monitoring changes in the UV band at 341 nm as a function of added anion concentration. The resulting decrease in intensity was fit using eq 1, as described by Connors.23
∆A/b ) (QtK∆[L])/(1 + K[L]) (1) Here, ∆A refers to the change in absorbance from the initial value, Qt is the total concentration of 1, K is the binding constant, ∆ is the change in extinction coefficient between the bound and unbound species, and L is the concentration of anion titrated.
10.1021/ja992579a CCC: $18.00 © 1999 American Chemical Society Published on Web 10/23/1999
Communications to the Editor
J. Am. Chem. Soc., Vol. 121, No. 44, 1999 10439
Table 1. Anion Binding Constants (Ka) for Compounds 1-4a FH2PO4Cl-
1b
3
4
2c
18200 M-1 60 M-1 50 M-1
118000 M-1 80 M-1 65 M-1
120 M-1
